Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Affiliated Tumor Hospital of Guangzhou Medical University, Guangzhou, China.
Eur J Surg Oncol. 2018 Jul;44(7):1087-1093. doi: 10.1016/j.ejso.2018.04.017. Epub 2018 Apr 27.
Regulatory factor X1 (RFX1) deletion has been reported to be correlated with poor prognosis of some types of cancer. The present study aimed to investigate the prognostic value of RFX1 in HCC, especially in small hepatocellular carcinoma.
Immunohistochemical assay was used to investigate RFX1 expression in 221 HCC tissues and another validation cohort of 71 small HCC samples. We also performed in vitro experiments to investigate if RFX1 regulated invasive capacity of HCC cells and expression of epithelial-mesenchymal transition (EMT) markers.
We found that RFX1 expression was significantly lower in HCC tissues compared to the corresponding non-tumor tissues. Further survival analysis suggested that the downregulation of RFX1 correlated with poor prognosis and a high recurrence risk in HCC patients, particularly in small HCC patients. Furthermore, another validation cohort of small HCC samples confirmed that downregulation of RFX1 in HCC tissues predicted high recurrence risk and poor prognosis for early stage HCC patients. In vitro studies suggested that knocking down RFX1 facilitated HCC cell invasion, while overexpression of RFX1 reduced the invasion of HCC cells. Western blot assays also indicated that RFX1 regulated expression of some EMT markers. Knocking down RFX1 decreased E-cadherin and increased vimentin expression, while RFX1 overexpression enhanced E-cadherin and decreased vimentin expression.
Our study demonstrated that RFX1 downregulation is a new predictive marker of high recurrence risk and poor prognosis of HCC; It has potential to help guide treatment for postoperative HCC patients, especially for small HCC patients.
已有报道称，调节因子 X1（RFX1）缺失与某些类型癌症的预后不良相关。本研究旨在探讨 RFX1 在 HCC 中的预后价值，尤其是在小肝细胞癌中的价值。
采用免疫组织化学法检测 221 例 HCC 组织和另外 71 例小 HCC 样本中的 RFX1 表达。我们还进行了体外实验，以研究 RFX1 是否调节 HCC 细胞的侵袭能力和上皮-间充质转化（EMT）标志物的表达。
我们发现，与相应的非肿瘤组织相比，RFX1 在 HCC 组织中的表达明显降低。进一步的生存分析表明，RFX1 的下调与 HCC 患者的预后不良和高复发风险相关，尤其是在小 HCC 患者中。此外，另一小 HCC 样本验证队列证实，HCC 组织中 RFX1 的下调预示着早期 HCC 患者的高复发风险和预后不良。体外研究表明，敲低 RFX1 促进 HCC 细胞侵袭，而过表达 RFX1 则降低 HCC 细胞的侵袭能力。Western blot 检测还表明，RFX1 调节一些 EMT 标志物的表达。敲低 RFX1 降低了 E-钙黏蛋白的表达，增加了波形蛋白的表达，而过表达 RFX1 则增强了 E-钙黏蛋白的表达，降低了波形蛋白的表达。
本研究表明，RFX1 的下调是 HCC 高复发风险和预后不良的新预测标志物；它有可能帮助指导 HCC 术后患者的治疗，尤其是小 HCC 患者。
